Planarians activate their regenerative power to circumvent carcinogenesis: an in vivo and in vitro approach to investigate the role of stem cell potency

Abstract

Planarians, such as Schmidtea mediterranea, are flatworms that are capable of regenerating any missing body region. They show an extensive regenerative ability and are able to circumvent tumor formation. Even under strong carcinogenic conditions, tumors were never observed. Regeneration in S. mediterranea is due to undifferentiated pluripotent stem cells. It is likely that these adult stem cells have a role in the evasion of tumor formation. The process of regeneration is mediated by neoblasts, which is a proliferative cell population that contains pluripotent stem cells.

We hypothesized that during carcinogenic exposure in S. mediterranea, pluripotent stem cells activate specific damage responses to provoke the circumvention of carcinogenesis. Focusing on differentiation processes and DNA repair, it could be that stem cells with high potency have better DNA repair mechanisms, explaining the effective response to carcinogens.

To address this hypothesis, in vivo experiments were performed to define whether the differentiation process is altered after carcinogen exposure and whether DNA repair mechanisms play a role in this alteration. Since stem cells possibly play an important role in the circumvention of cancer and to support this in vivo approach, cell culture conditions were optimized.